Brain (2000), 123, 620–640
Functional MRI evidence for a role of frontal and
inferior temporal cortex in amodal components of
priming
Randy L. Buckner,1,3 Wilma Koutstaal,2 Daniel L. Schacter2 and Bruce R. Rosen1
1Department
of Radiology, Massachusetts General
Hospital, Nuclear Magnetic Resonance Center,
Charlestown and Department of Radiology, Harvard
Medical School, 2Department of Psychology, Harvard
University, Cambridge and 3Departments of Psychology,
Radiology, and Anatomy and Neurobiology, Washington
University, St Louis, Missouri, USA
Correspondence to: Dr Randy L. Buckner, Department of
Psychology, Washington University, Campus Box 1125,
One Brookings Drive, St Louis, MO 63130, USA
E-mail: [email protected]
Summary
Changes in human brain activity associated with
repetition priming during word generation were
characterized across a series of neuroimaging and
behavioural studies. Repetition priming was consistently
observed behaviourally as a decrease in response latency
for repeated items, and was found for both visually and
aurally cued word-generation tasks. Brain imaging using
whole-brain functional MRI identified neural correlates
of these effects. The principal effect of priming was to
reduce neural activity within regions that were already
being used to perform the word-generation tasks.
Repeated word generation in response to visual cues
was correlated with anatomically selective reductions in
activity within the left frontal cortex along the inferior
frontal gyrus and inferior temporal regions and, to a
lesser degree, in specific earlier visual regions. These
reductions were reversed when new items were presented,
indicating that they were item-specific. Repeated word
generation in response to aural cues also showed
anatomically selective activity reductions within the left
frontal and inferior temporal regions, indicating that
these activity reductions were not dependent on the
perceptual modality of the cue. The auditory cortex
showed minimal repetition-related reductions. The
presence of activity within left frontal regions that
decreases as a function of item repetition for both visual
and auditory cues suggests that these reductions may
underlie an amodal repetition-priming effect existing at
processing stages involving lexical/semantic search and
access. The surprising finding that activity reductions in
the inferior temporal cortex can be linked to repetition
of either visual or auditory cues further suggests that
these regions may be modulated in a top-down fashion
during repetition priming, independent of (or in parallel
with) stimulus-driven perceptual processes. Taken
collectively, the data converge on a neural correlate of
lexical/semantic priming. Amodal lexical/semantic
processes, which may be triggered initially by modalityspecific cues, proceed via an interaction between frontal
and posterior brain regions. These interdependent regions
show activity reductions that correlate with facilitated
task performance when items are repeated.
Keywords: priming; memory; learning; neuroimaging; frontal cortex; inferior temporal cortex; prefrontal cortex; implicit
memory
Abbreviations: ANOVA ⫽ analysis of variance; BA ⫽ Brodmann area; fMRI ⫽ functional MRI; SPGR ⫽ spoiled gradient echo
Introduction
Brain imaging methods based on PET and functional MRI
(fMRI) have been used recently to characterize the regions
involved in word-retrieval tasks and to determine how the
level of activity within these regions may change when items
are repeated. Both PET and fMRI studies have shown that
word-retrieval tasks that depend on meaning-based (semantic)
© Oxford University Press 2000
decisions or phonological decisions are most often
accompanied by increased activation in several spatially and
functionally diverse regions (for reviews, see Wise et al.,
1991; Petersen and Fiez, 1993; Warburton et al., 1996; Binder
et al., 1997; Cabeza and Nyberg, 1997). In addition to
increased activation in modality-specific brain regions
fMRI evidence for amodal components of priming
involved in the initial perception of the stimuli used to cue
task performance (e.g. activation in the visual cortex in the
case of visually presented words or other items), wordretrieval tasks often activate regions of the left inferior frontal
gyrus at or near Brodmann areas (BA) 44, 45 or 47, sometimes
extending in an anterior and dorsal direction along the border
of the prefrontal and motor cortex (BA 44 or 6). Activations
in the anterior cingulate, right lateral cerebellum and left
temporal cortex are also commonly observed.
These regions play some role in operating on and/or
maintaining higher-level verbal representations. However, the
specific role is unclear at present and may relate to aspects
of phonology, lexical representations and/or their integration
with semantics; subregions within the larger networks
probably provide separate processing contributions. What is
clear is that, across a wide range of tasks that demand
elaboration upon verbal and semantic representations, this
network of higher-level regions that includes the frontal
cortex is consistently activated and is largely independent of
the specific modality of the cue (e.g. Chee et al., 1999) or
even whether the cue is a picture or visual word (e.g.
Vandenberghe et al., 1996). Moreover, these regions can be
modified by experience. When subjects retrieve the same
words repeatedly or make the same semantic meaning-based
decision on multiple occasions, activity within these regions
is attenuated (Raichle et al., 1994; Demb et al., 1995).
The observation that these regions can be modified by
experience is particularly critical for the understanding of
human memory. Behavioural indices, such as response latency
and accuracy, have shown that when items are repeated
during semantic or lexical retrieval (or decision tasks),
performance on the repeated items is faster, more accurate,
and/or biased—a phenomenon referred to as repetition
priming. Expanding beyond the early studies of Raichle and
colleagues and Demb and colleagues, mentioned above,
numerous studies have shown that brain regions that are
active during the initial performance of a semantic or lexical
retrieval task are less active after repeated exposures to the
items (Squire et al., 1992; Raichle et al., 1994; Buckner
et al., 1995a; Demb et al., 1995; Blaxton et al., 1996;
Gabrieli et al., 1996; Schacter et al., 1996). These reductions
may reflect a neural correlate of repetition priming
(Ungerleider, 1995; Schacter and Buckner, 1998; Wiggs
and Martin, 1998). Repetition-related reductions have been
observed in the frontal cortex and in the other regions
mentioned above, as well as in earlier visual regions
associated with perceptual processes.
Recent investigations have focused on understanding which
specific brain regions show priming-related activity
reductions and what kinds of task processes are correlated
with these reductions. These explorations are, in part,
motivated by the behavioural observation that repetitionpriming effects can be reduced, but are typically not
eliminated, when the perceptual characteristics of a repeated
item are changed between study and test. For example,
priming effects are often reduced when an item is presented
621
first in the visual and then in the auditory modality, or when
characteristics of an item within a given modality are altered
(Roediger and McDermott, 1993; Schacter et al., 1993).
Behavioural observations indicating that priming may often,
to a greater or lesser degree, survive changes in the specific
perceptual format of the stimulus suggest that priming
involves both form-specific and non-specific or amodal
mechanisms (Kirsner et al., 1989; Rajaram and Roediger,
1993), possibly involving processes occurring at multiple
stages in a processing hierarchy (Roediger et al., 1999)
and/or multiple brain regions within processing subsystems
(Schacter and Tulving, 1994). Perceptual processing regions
that are sensitive to the perceptual format of a stimulus and
higher-level, conceptual processing regions that are relatively
less influenced by the precise perceptual instantiation of a
word or concept may both benefit from item repetition.
That is, repetition priming may modify activity both within
relatively early brain regions involved in perceptual processes
and in regions occurring later in the hierarchy of processing,
at more conceptual stages that promote lexical and semantic
access. Anterior brain regions, including the left frontal
cortex discussed above, provide a prime candidate for regions
likely to be involved in conceptual aspects of repetition
priming; more posterior modality-specific regions in the
visual or auditory cortices may be involved in perceptual
aspects of priming.
In the present study, two related questions were explored
using functional neuroimaging techniques: (i) to what extent
are brain regions that are believed to be involved in amodal
(conceptual) processing modulated by repetition priming?
(ii) to what extent are brain regions that are believed to
subserve modality-specific processes modulated by
repetition? These questions were addressed in a series of
fMRI studies using both visually and aurally cued tasks. All
of these studies involved word-generation tasks that have
been used previously with PET. Because these wordgeneration tasks can cause motion artefacts when overt speech
is employed, we adopted a covert procedure in which subjects
generate words silently. Accordingly, a series of behavioural
studies outside the MRI environment was also conducted to
characterize the behavioural correlates of repetition priming
in these covert tasks, and to build confidence that the
paradigms imaged using fMRI yielded robust repetitionpriming effects under covert word-generation procedures.
Methods
Overview
Subjects performed word-generation tasks within the MRI
environment or outside the MRI environment, in a behavioural
setting typical of cognitive psychological studies. Cues to
guide word generation (most often the beginnings of words
or word stems) were presented in blocks. A given block
consisted either entirely of new items (cues that were never
previously presented in the experiment) or entirely of repeated
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R. L. Buckner et al.
Table 1 Overview of studies
Study
Type
n
Stimuli
Modality
Task
Response mode
1a
1b
1c
2a
Beh
Beh
fMRI
Beh
12
12
8
12
2b
fMRI
8
3a
3b
3c
Beh
Beh
fMRI
12
12
12
Word stems
Word stems
Word stems
Word stems
Nouns
Word stems
Nouns
Word stems
Word stems
Word stems
Visual
Visual
Visual
Visual
Visual
Visual
Visual
Auditory
Auditory
Auditory
Word completion
Word completion
Word completion
Word completion
Verb generation
Word completion
Verb generation
Word completion
Word completion
Word completion
Overt
Overt and covert
Covert
Overt
Overt
Covert
Covert
Overt
Overt and covert
Covert
Beh ⫽ behavioural study; n ⫽ number of subjects participating in substudy.
items (cues that were presented previously, in earlier blocks
of the experiment). Within the MRI environment, brain
activity was indirectly measured using an fMRI sequence
sensitive to blood oxygenation level-dependent contrast
(Kwong et al., 1992; Ogawa et al., 1992); all word generation
was performed covertly. In the behavioural setting, voice
onset latencies of word generation were measured to provide
a behavioural index of repetition priming. Critically, in the
behavioural setting both covert and overt word-generation
procedures were used to determine their comparability.
Methods that are general to all of the studies are described
first, followed by the methods and results pertaining
specifically to each of the five behavioural and three fMRI
studies. Table 1 provides an overview of the studies, including
the type of study (behavioural or fMRI), the nature of the
stimuli, the presentation modality, the word-generation task
performed and the response mode (overt, covert or both). As
indicated in Table 1, the studies were organized into three
sets of experiments and subexperiments: experiments 1a–c
focused on visual word-stem completion, experiments 2a–b
compared visual word-stem completion with visual verb
generation, and experiments 3a–c examined auditory wordstem completion.
Subjects
All subjects were native speakers of English between the
ages of 18 and 37 years. The number of participants included
in the three fMRI experiments were as follows: eight in
fMRI experiment 1 (six males); eight in fMRI experiment 2
(four males); and 12 in fMRI experiment 3 (six males). All
fMRI subjects were right-handed, as assessed using the
Edinburgh Handedness Inventory (Lezak, 1995). For the
behavioural studies, 12 naive subjects between the ages of
18 and 35 years served in each study. Informed consent was
obtained prior to scanning or testing in a manner approved
by the Human Studies Committee of the Massachusetts
General Hospital.
Behavioural methods
Visual stimuli were presented using a PowerMacintosh (Apple
Computer) connected to a Sharp 2000 colour LCD projector.
For fMRI, stimuli were projected onto a screen attached to
the head coil through a collimating lens. For the auditory
study, subjects wore a custom-modified headphone connected
to an amplifier outside the MRI suite. Sounds were presented
by the PowerMacintosh computer and fed directly into the
amplifier. In the behavioural setting, stimuli were displayed
on a 17-inch AppleVision monitor. Voice onset latencies
were recorded through a CMU button box (Carnegie Mellon
University, Pittsburgh, Pa., USA). Sounds were presented
using AppleDesign Powered Speakers (Apple Computer).
MR imaging methods
Scans were acquired on a 1.5 T General Electric scanner
fitted with an echo-planar imaging upgrade (Advanced NMR
systems, Wilmington, Mass., USA). Whole-brain imaging
was performed using the standard General Electric quadrature
head coil.
Subjects lay in the scanner with the head snugly surrounded
by a pillow and cushions within the head coil to reduce
movement. The scanning procedure involved first collecting
anatomical images and adjusting the echo-planar shim (Reese
et al., 1995). This non-functional portion of the session
(~30 min) was directly followed by eight to 10 functional
runs of 3.5 min each (⬍1 h 30 min).
Two relevant anatomical images were collected, including:
(i) a sagittal localizer image [conventional T1-weighted
spoiled gradient echo (SPGR) sequence, 60 contiguous
2.8 mm slices) and (ii) an echo-planar T1-weighted inversion
recovery image aligned to the functional runs [TI (inversion
time) ⫽ 1200 ms, 1.563 ⫻ 1.563 mm in-plane resolution].
Functional runs involved scanning over 16 or 17 transverse
slices (7 mm, skip 1 mm between slices, 3.125 ⫻ 3.125 mm
in-plane resolution) aligned to the plane intersecting the
anterior and posterior commissures. The resulting 12.8 or
13.6 cm range of imaging was sufficient to image the entire
brain, including the cerebellum, in almost every subject.
Between 105 and 128 images per slice were acquired using
a T2*-weighted asymmetrical spin echo sequence designed
to reduce contributions from large vessels [TE (echo time) ⫽
70 ms, 25 ms offset] (Baker et al., 1993). A set of four or
more sequential images were generated and discarded before
fMRI evidence for amodal components of priming
the critical image acquisition was begun in order to allow
saturation of T1.
Generation of individual subject activation maps
All fMRI runs for an individual subject were averaged
vertically, such that each time-point was the average of that
same time-point across runs. For example, if six runs were
collected from a subject, the images acquired at the 8 s timepoint in each of the six individual runs were averaged to
yield one set of images at 8 s, each image representing the
mean of the six contributing images.
Runs averaged within a subject were used to construct
a statistical activation map based on the non-parametric
Kolmogorov–Smirnov statistic (Press et al., 1992). Either all
task blocks were compared with fixation blocks, or the task
blocks of novel items were directly compared with blocks
of repeated items (similar to Buckner et al., 1998a, b;
Wagner et al., 1998). Statistical maps were displayed using
a pseudocolour scale superimposed on the high-resolution
EPI (echo-planar imaging) T1-weighted inversion recovery
image, which was acquired in-plane and aligned to the
functional activation runs.
Generation of group activation maps in
Talairach space
Each individual subject’s data were transformed into the
stereotaxic space of the Talairach and Tournoux atlas
(Talairach and Tournoux, 1988) using procedures described
previously (Buckner et al., 1998a, b). Once in atlas space,
data were averaged across subjects. First, the interpolated
SPGR images were averaged to yield a mean anatomy image.
Secondly, the functional runs were averaged and used to
construct activation maps in a manner identical to that
used for individual subjects. In this instance, however, the
interpolated and averaged SPGR images were used as an
anatomical underlay.
Identification of peaks in standardized atlas
coordinates and time-course generation
Coordinates of activation peaks were determined using an
automated peak detection algorithm. Peaks were defined as
the location of voxels (i) showing significant activation (P
⬍ 0.0001), (ii) showing more significant activation than
neighbouring voxels, and (iii) occurring within a cluster of
at least five significant voxels. These procedures have been
set so as to identify few false positives in control data sets
using the logic of Zarahn and colleagues (Zarahn et al.,
1997; see also Buckner et al., 1998b). The location of the
most significant voxel was selected in instances in which
peaks were identified within 8 mm of each other. However,
because of uncertainties in any statistical-threshold procedure
owing to coloured-noise properties such as motion, the time-
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course of the signal change was characterized for all peaks
of theoretical interest to determine whether the signal change
followed the task paradigm (Binder and Rao, 1994).
Regions were defined around these peaks using a second
automated procedure to track the signal change within that
region over time. For this procedure, all contiguous significant
voxels within 12 mm of the peak location were included in
a 3D volume. Mean signal intensity within this volume was
calculated for each image over the averaged functional runs,
yielding a time-course for the signal change. The time-course
was corrected for linear drift and temporally smoothed with
a 6 s Hanning filter. The time-course was then scaled to
percentage signal change.
Individual experiments and results
Experiment 1a: visually cued overt word-stem
completion
Repetition-priming effects were examined in an overt visually
cued variant of the word-stem completion task. Subjects were
presented visually with three-letter word stems, one at a time
(e.g. ‘gre_’ or ‘pur_’), and were instructed to generate aloud
the first English language word completion that came to
mind (e.g. ‘green’ or ‘purple’). Word stems were selected
from a pool of 288 unique three-letter word stems that had
at least five English word completions. Word stems were
presented centrally in white-on-black letters, in 36-point
Geneva font. The stimulus duration was 2.0 s, with 2.5 s
between the onsets of stimuli. Behavioural testing was
conducted in experimental runs in which blocks of multiple
stimuli were presented sequentially and repeatedly, across a
given run (12 stimuli in each 30 s block). Each block
contained stimuli that were presented in a different random
order each time. The stem-completion blocks were separated
by a 30 s period of visual fixation. In this manner, a series
of word-stem completion blocks was performed with items
within the blocks having been exposed for differing numbers
of repetitions across blocks. In the first block the word stems
were new (NEW), in the second they were repeated once
(REP1), in the third they were repeated twice (REP2), etc.
for a total of five blocks. Six runs were conducted for each
subject. This paradigm is identical to fMRI experiment 1c
except that, in the behavioural study, subjects responded
overtly to each word-stem cue.
Experiment 1a: results
Clear repetition-priming effects were observed (Fig. 1). The
mean reaction time for NEW word-stem completions (the
first block) was 902 ms. Responding became progressively
faster across repetitions, decreasing to 726 ms by the final
block. A repeated measures ANOVA (analysis of variance)
performed on the mean voice onset latencies for the five
blocks showed a highly significant effect of repetition
[F(4,44) ⫽ 16.57, P ⬍ 0.0001)].
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R. L. Buckner et al.
Fig. 1 Overt visual word-stem completion. Repetition priming in
experiment 1a was revealed as a speeded response across blocks
when items were repeated. Mean voice onset latency is plotted for
each block as a diamond. NEW ⫽ block of items comprising
entirely word stems that were not previously presented; REP1 ⫽
block of items where all stems were previously presented once;
REP2 ⫽ items previously presented twice, etc. The line is the
best log fit for the data.
Examination of participants’ response stereotypy revealed
that, on average, subjects provided the same completions to
the stems on 87% of the trials (SD ⫽ 0.09, range ⫽ 0.72–
0.98; calculated as the sum of the most frequently repeated
responses for each item). Furthermore, in this experiment
and all subsequent behavioural experiments, significantly
greater decreases in response times were found for those
items where subjects provided the same response to the
repeated cues than for those occasional items where they
generated a novel response to the repeated cues (and which
showed response times similar to those of never-presented
NEW items). This suggests that priming depended on
repetition of both the cue and the lexical/conceptual processes
involved in generating the response.
Experiment 1b: visually cued overt and covert
word-stem completion
In order to determine whether covert word-stem completion
would yield repetition-priming effects similar to those of
overt word-stem completion, a behavioural study was
conducted using a within-subjects design in which, across
runs, subjects generated words either overtly or covertly
(three runs of each kind). For the covert runs, subjects did
not speak aloud during the initial repetition blocks but silently
generated a single-word completion for each cue as it was
presented. The response was then switched to overt production
after four item repetitions so that the repetition-priming effect
could be assessed. As in the subsequent fMRI studies,
which also involved covert rather overt word generation, the
instructions to participants were specific, requiring subjects
to covertly generate a response for each item that was
presented.
In addition, to allow the estimation of voice-onset latencies
for the new items in the covert runs, prior to the first block
Fig. 2 Overt and covert visual word-stem completion. Repetition
priming in experiment 1b was again revealed as a speeded
response across blocks. Mean voice onset latency is plotted for
each block as a diamond, similar to Fig. 1. The filled diamonds
indicate overt task blocks; open diamonds indicate covert task
blocks. The lines are the best log fit for the data, with the initial
latency for the covert blocks estimated from the PRE block (all
items NEW). Overt and covert repetitions gave a similar increase
in speed of responding.
an additional set of new items was presented. For this
prerepetition block, subjects responded overtly for both overt
and covert word-production runs. This allowed estimation of
the beginning of the voice-onset latency for subjects during
the covert word-production runs but without participants ever
overtly producing items in the critical covert blocks. Similarly,
the final block (REP4) was performed overtly for both the
overt and covert word-production runs, allowing the effect
of item repetition to be assessed in both instances. For all
runs (both overt and covert), participants were instructed, via
a visual cue presented immediately before each block, whether
the block was to be ‘spoken’ or ‘silent’. The basic question
was: would runs involving covert word production show the
same item-repetition effects as those involving overt word
production? Finally, a final overt block of repeated items
(REP5) was added as a further control so that subsequent
learning could be assessed in the covert blocks following the
adoption of an overt response.
Experiment 1b: results
Again, clear repetition-priming effects were observed for
overt word production (Fig. 2). Importantly, item repetition
effects were also clearly observed for covert production;
there was little difference between the covert and overt runs.
The mean reaction time for completions to the NEW wordstems was 858 ms for the overt runs and was estimated to
be 842 ms for the covert runs (based on the PRE repetition
block). In the overt condition, responding became
progressively faster across repetitions, reducing to 677 ms
by the fourth repetition block. As shown in Fig. 2, covert
repetition yielded a similar repetition-priming effect,
decreasing to 649 ms by the fourth repetition. The final, overt
fifth repetition block yielded only slightly faster latencies for
fMRI evidence for amodal components of priming
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Table 2 Selected foci of activation across studies
Region
Exp 1c: vis stem
Exp 2b: stem ⫹ verb
Exp 3c: aud stem
x
x
y
z
x
y
z
–37
–28
–50
–6
0
15
43
9
28
–58
3
16
–68
–62
37
12
–12
65
65
–34
–21
–40
–28
–43
–3
3
12
28
6
22
–52
–3
13
–68
–58
34
9
–12
59
50
–21
–21
–43
–43
–43
–53
–43
9
34
–33
–52
–46
34
3
–9
–9
–6
–43
–34
–56
6
31
–43
25
3
0
y
z
Task conditions greater than low-level control
L frontal
–34
9
34
L operculum
–28
22
12
L inferior temporal
–37
–55
–18
SMA/preSMA
0
0
56
6
9
56
R cerebellum
12
–65
–31
34
–65
–21
NEW greater than REPEATED
L frontal
L operculum
L inferior temporal
Selected Talairach and Tournoux (1988) coordinates (x, y, z) are given for areas of greatest significance
and generalization across studies. All coordinates listed designate regions of highly significant
activation. A full list of coordinates is available upon request from the authors. SMA ⫽ supplementary
motor area; vis ⫽ visual; aud ⫽ auditory; L ⫽ left; R ⫽ right.
both the overt and covert runs, indicating that the majority
of the repetition-priming effect had been attained for both
procedures.
A repeated measures ANOVA performed on the mean
voice-onset latencies for the overt blocks, and including only
the items from the repetition phase (i.e. items that were the
same across the blocks, or the conditions NEW, REP1, REP2,
REP3, REP4 and REP5 from Fig. 2) showed a highly
significant overt repetition effect [F(5,55) ⫽ 19.91, P ⬍
0.0001]. Importantly, a similar analysis for the covert blocks
also showed an effect of repetition [considering only the
PRE-NEW and REP4 blocks, F(1,11) ⫽ 124.96, P ⬍ 0.0001;
considering PRE-NEW, REP4 and REP5, F(2,22) ⫽ 84.47,
P ⬍ 0.0001].
Thus, by all measures used, the covert procedure yielded
a repetition-priming effect that was robust and comparable
with that of the overt production procedure. These findings
suggest that (i) participants are generating words during the
covertly cued blocks, and (ii) the processes underlying
repetition priming occur under covert conditions.
Experiment 1c: fMRI of visually cued wordstem completion
The basic task paradigm was a covert variant of the wordstem completion task as used in behavioural experiments of
the repetition-priming effect, and also as previously used
with PET (Squire et al., 1992; Buckner et al., 1995a; Schacter
et al., 1996) and fMRI (Buckner et al., 1996a; Ojemann
et al., 1998) studies. Two types of fMRI run were studied.
In the first six runs for each participant, 30 s blocks of wordstems were presented with all new items in each block. The
goal of these runs was to determine the functional–anatomical
brain regions recruited during the word-stem completion task,
independently of item-specific repetition-priming effects. The
TR (repetition time) was set to 2.0 s. The second type of run
was identical to that of experiment 1a, and comprised the
final four runs for each participant. For these runs, the same
set of word-stem cues was presented repeatedly across a
series of five blocks. The TR was set to 3.0 s. The overall
presentation parameters were identical to those of experiment
1a, except that the participants performed covert word-stem
completion as described in experiment 1b.
Word-stem completion was contrasted with a low-level
reference task in which subjects simply visually fixated on a
centrally presented cross-hair. Fixation occurred for 30 s
before and after each block of word-stem completion.
Experiment 1c: results
Main effect of task
A network of brain regions was active during word-stem
completion when compared with fixation, confirming results
from prior PET and fMRI studies (Buckner and Tulving,
1995; Ojemann et al., 1998) (Fig. 3, Table 2). This network
included statistically significant activations within the visual
cortex extending from medial regions that are likely to lie
within the striate cortex to extrastriate regions to regions
within the inferotemporal cortex; these extrastriate activations
extended further in the anterior direction in the left than in
the right hemisphere. Multiple frontal regions were active,
including a dorsal frontal region within the inferior frontal
gyrus near BA 6 and/or 44 and a ventral frontal (prefrontal)
region within and lateral to the opercular cortex (at or
near BA 44 and/or 45). Along the medial wall of the
frontal cortex, activations were noted in supplementary
motor area, extending into the anterior cingulate. The right
lateral cerebellar cortex also showed prominent activation.
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R. L. Buckner et al.
Fig. 3 fMRI of visually cued word-stem completion. Data from experiment 1c show the pathway of brain regions activated during wordstem completion when compared with fixation. Sections were taken horizontally; the inferior–superior level is given below each section
based on the plane in the Talairach and Tournoux atlas (Talairach and Tournoux, 1988). Coloured voxels are all significant (threshold ⫽
P ⬍ 0.001); increasing significance is revealed by increasing colour intensity. A pathway of regions is activated, including left frontal
regions along the inferior frontal gyrus (A, D and E), the supplementary motor area extending into the anterior cingulate (B), the lateral
parietal cortex (C), the visual striate cortex extending into the extrastriate cortex and inferior temporal cortex (F), and the right lateral
cerebellum (G).
A complete list of all active regions, their coordinates in
Talairach and Tournoux atlas space (Talairach and Tournoux,
1988) and their significance can be obtained from the
first author.
Repetition effects
To determine the correlates of repetition priming, the mean
fMRI signal intensity was tracked across the new and repeated
item blocks for a subset of regions that were activated by
the task during initial runs (in which no items were repeated).
The findings are shown in Fig. 4. Multiple regions, including
those within the visual extrastriate cortex and the two regions
within the left inferior frontal gyrus, decreased significantly
for the repeated compared with the new items. Thus, the first
three studies converge to demonstrate related correlates of
repetition priming. Experiments 1a and 1b clearly revealed
decreases in response latency as a function of repeated
performance of the word-stem completion task, and the
present experiment showed that these decreases were
accompanied by reductions in the level of neural activation
observed in specific regions of the pathway that is activated
during word generation.
However, the present experiment contained two
confounding factors. First, it is possible that the gradual
reduction in fMRI signal that we observed for the left frontal
regions partly or entirely derives from non-specific factors,
such as fatigue, that are unrelated to item repetitions.
Secondly, examination of the time-course of the fMRI signal
revealed a signal undershoot that caused shifts in the baseline
that could account for part or all of the signal reductions
(e.g. the component labelled b in Fig. 4).
Confidence in the item-specific nature of the effects that
we observed would be increased if it could be shown that
(i) the reductions were specific to the particular sets of items
that were repeated and did not generalize to new (not
previously presented) items, and (ii) similar magnitudes and
patterns of reduction occur under conditions in which multiple
new blocks of items are included at the beginning of the
runs, such that the fMRI signal undershoot would be stable
before presentation of the first repetition block. The first
of these aims was addressed in experiment 2a, in which
participants received both a modified version of the visual
stem-completion paradigm and performed an additional verbgeneration task (described below) in a behavioural setting;
the second aim was addressed in experiment 2b, in which
both the modified visual stem-completion and verb-generation
paradigms were presented during functional imaging.
Moreover, because new and repeated item blocks were
examined within the same fMRI runs in experiment 2b, the
separate item types could be compared directly in order
to reveal the complete anatomy showing repetition-related
modulation. It was not possible to perform this analysis in
the present experiment.
Experiment 2a: overt visually cued word-stem
completion and verb generation
Word-stem completion
In the modified visual word-stem completion paradigm, voiceonset latencies were examined when words were generated in
response to visually presented word stems in a total of four
runs. Each run comprised blocks of items that were repeated
from previous blocks (similar to experiments 1a–c) but, in
addition, they also included blocks of items at the beginning
and the end of the run that were entirely new (never previously
presented). Specifically, each run began with two blocks of
new items, then items from the second block were repeated
four times, after which there were two further blocks of new
items (i.e. runs followed the following structure: NEW, NEW,
REP1, REP2, REP3, REP4, NEW, NEW). The block length
was decreased to 16 s and included seven items per block
(stimulus duration ⫽ 1.5 s with 2.3 s between stimulus
onsets). The key question was: will response latencies for
the two blocks of new items at the conclusion of each run
be similar to the response latencies for new items at the
beginning of the run? If, as expected, response latencies
abruptly increased upon changing from the repetition phase
of the run to the presentation of new items, this finding
fMRI evidence for amodal components of priming
Fig. 4 fMRI signal changes for theoretically important regions. (A) A region within the left inferior
frontal gyrus (–34, 9, 34). (B) An extrastriate region extending into the inferior temporal gyrus (–37,
–55, –18). (C) A region at or near the striate cortex (lingual gyrus; 0, –93, –9). In each panel, the
horizontal image to the left shows the area of the region in one plane. Regions were defined in three
dimensions (see text). The time-course to the right shows the signal intensity over time for the region.
Signal intensity is in percentage change and the positions of the task blocks are indicated at the bottom
of the graph. Labels indicate word-stem completion task blocks. NEW indicates new items; REP1,
REP2, REP3 and REP4 indicate blocks with items presented previously as described in the text and
similar to Figs 1 and 2; ⫹ indicates fixation. In all three regions, signal intensity decreased with
increasing repetition, as shown for the frontal region (a). However, a possible confounding factor
existed in that the baseline signal was also changed between blocks during the fixation baseline (b).
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would provide evidence for the item-specific nature of the
behavioural facilitation effects we observed.
Verb generation
The observation in experiment 1c of repetition-related
decreases in brain activation in amodal processing regions,
particularly the left prefrontal cortex along the inferior frontal
gyrus, suggests that the word-generation task reveals neural
correlates of facilitated task processing in regions that are
involved in higher-level aspects of lexical or semantic
response generation and selection. However, in visually cued
word-stem completion, retrieval occurs under conditions in
which the stimulus cue (the three-letter word stems) provides
comparatively direct perceptual support for word retrieval
(but note that, because the word stems all allowed multiple
completions, some selection as well as generation is clearly
necessary). Examination of a task in which the stimulus cue
does not provide any direct perceptual support for the
response to be retrieved, and in which the relationship
between the cue and the word to be generated is strictly
semantic or conceptual in nature, would allow generalization
of the findings from the stem-completion task. Investigating
such a task would also establish more firmly that the
repetition-related reductions that we observed are associated
with repeated semantic, conceptual or lexical processing. A
suitable task for these purposes is verb generation, which
has been used previously in PET studies (e.g. Petersen et al.,
1988; Wise et al., 1991; Raichle et al., 1994; Warburton
et al., 1996). In the verb-generation task, participants are
shown nouns (e.g. ‘dog’) and are asked to generate a verb
that might be associated with the noun (e.g. ‘walk’ or ‘bark’).
As for visually presented word stems, the effects of
repeated generation of verbs (action words) associated with
nouns were assessed in an identical behavioural study that
paralleled the word-stem study in design. All subjects
performed both visual word-stem completion and verb
generation, counterbalanced for order across subjects.
Experiment 2a: results
Word-stem completion
From Fig. 5 it is clear that the effects of repetition in the
visual word-stem completion task were largely specific to
the sets of repeated items: the mean voice-onset latencies for
the first new blocks were very similar to one another (1002
and 1008 ms, respectively). These latencies were also similar
to the concluding blocks of new items within each run (1029
and 1016 ms, respectively). Only the blocks in which
the items were repeated showing systematically decreasing
response times, decreasing to 870 ms by the fourth repetition.
A repeated measures ANOVA, performed on the mean voice
onset latencies in which only the blocks from the phase
where there was repetition of the same items were considered,
showed a significant effect of repetition [F(4,44) ⫽ 8.63,
Fig. 5 Repetition priming for visual word-stem completion in the
modified block design of experiment 2a. The NEW item blocks in
the PRE phase showed similar mean onset latencies. During the
REPETITION phase the response times decreased, revealing a
behavioural correlate of priming. Critically, in the POST phase,
when NEW items were again introduced, the response time
increased to a level indistinguishable from that for the PRE phase,
suggesting the repetition-priming effects were item-specific. The
line is a log fit to the data acquired during the REP phase.
P ⬍ 0.0001]. In contrast, an ANOVA comparing the mean
voice-onset latency for the first two NEW blocks versus that
for the last two NEW blocks, provided no evidence of a
global or ‘item-independent’ within-run practice or fatigue
effect [F(3,33) ⬍ 1]; a similar conclusion could be drawn
from a focused comparison of the average of the first two
new blocks against the average for the last two new blocks
[F(1,11) ⬍ 1]. These comparisons indicate that the effects
of repetition in the visual stem-completion task are itemspecific, i.e. observed when the particular stems are repeated,
rather than as function of prolonged or additional performance
of the task.
As in the previous experiments, participants’ responses
showed a high level of stereotypy (mean ⫽ 86%, SD ⫽
0.08, range ⫽ 0.73–0.97) .
Verb generation
Repetition effects in the verb-generation task were clearly
present, and paralleled the pattern observed for the wordstem completion task (Fig. 6). Response times were longer
for new items for which participants were required to generate
an appropriate verb for the first time (mean voice-onset
latencies of 1267 and 1253 ms for the PRE NEW and NEW
items, respectively), but decreased with repeated performance
of the task, decreasing to 998 ms by the fourth repetition. A
repeated measures ANOVA performed on the mean voiceonset latencies for the blocks from the repetition phase, in
which the same items were presented repeatedly (i.e.
conditions NEW, REP1, REP2, REP3 and REP4), revealed
a significant effect of repetition [F(4,44) ⫽ 38.83, P ⬍
0.0001]. Plotting the number of repetitions against the mean
response time revealed that, as for the word-stem completion
fMRI evidence for amodal components of priming
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repetition. Thirdly, the repetition effects could be examined
after a baseline state had been established, following the
signal undershoot as observed in experiment 1c and many
prior fMRI studies. The signal rebound could be examined
for the NEW item blocks following REP blocks to determine
whether the repetition-related effects were indeed itemspecific.
Experiment 2b: results
Main effect of task for word-stem completion
Fig. 6 Repetition priming for visual verb generation in experiment
2a. The pattern of response was very similar to that found for
word-stem completion in Fig. 5. However, response times during
verb-generation were slightly longer.
task, performance facilitation was well described by a power
function (Fig. 6).
As found for the visual word-stem completion task, Fig.
6 shows that these decreases in response times were specific to
the particular items that were repeated. The two measurements
where new nouns were presented following the repetition
blocks (POST) were accompanied by a clear increase in
response latency, with response times (1226 and 1246 ms)
that were very similar to the initial response times (1267 and
1253 ms). There was no difference in the average latency of
responding to NEW items at the beginning of the runs versus
NEW items at the conclusion of the runs [comparing all four
blocks of NEW items, F(3,33) ⬍ 1; comparing the average
of the first two NEW blocks against the average of the last
two NEW blocks, F(1,11) ⬍ 1.8].
Consideration of participants’ responses showed that the
level of response stereotypy during the repetition phase was
again considerable (mean ⫽ 84%, SD ⫽ 0.08, range ⫽
0.67–0.96)
Experiment 2b: fMRI of covert visually cued
word-stem completion and verb generation
Functional imaging was performed during covert tasks that
were similar in format to those described in the behavioural
experiment 2a. Both word-stem completion and verb
generation were examined in separate runs. Prior to each
run, specific instructions were given to perform all task
blocks covertly. Ten functional runs (five for each task) were
acquired per subject, each run consisting of 16 interleaved
16 s blocks (TR ⫽ 2 s). The ordering of which sets of runs
came first (word-stem completion or verb generation) was
counterbalanced across subjects. This design allowed several
analyses beyond those possible in experiment 1c. First,
each type of block (NEW or REP) could be independently
compared with the same fixation blocks. Secondly, the NEW
and REP blocks could be directly compared with each other
to identify directly those regions that are modulated by item
Consistent with experiment 1c, a network of brain regions
was again activated by word-stem completion (all NEW
words), as contrasted with the low level-fixation control (Fig.
7, Table 2). These activations were located within multiple
left frontal and prefrontal regions (along the inferior frontal
gyrus), the visual striate and extrastriate cortex extending into
the inferior temporal cortex, and the right lateral cerebellum,
among others. For reasons that are not clear, these data
contained more noise of high spatial frequency (note the
speckled appearance of the data in Fig. 7).
Main effect of task for verb generation
The findings from verb generation were extremely similar to
those from word-stem completion. All of the activations
generalized, including left prefrontal activation extending
from both the inferior (near BA 44 and/or 45) and dorsal
portions of the inferior frontal gyrus (BA 44 and/or 6)
into more anterior prefrontal regions, including BA 47.
Surprisingly, there were few differences between the wordstem completion and verb-generation tasks (Fig. 7A and B).
On the one hand, this suggests that the present findings are
reliable across independent data sets from different tasks. On
the other hand, word-stem completion and verb generation
are different in terms of task demands (for discussion, see
e.g. Buckner et al., 1995b). It is thus noteworthy that the
two tasks activate similar anatomical regions, as revealed by
bold-contrast fMRI. In the present study, however, a powerful
means of comparing the word-stem completion and verb
generation tasks was not available to address directly whether
there were relatively subtle differences in the anatomical
regions recruited by these two tasks. This is because the
between-task comparison would be across runs. Results
of this comparison were explored but yielded no notable
differences. For purposes of further comparison of the
repetition-priming effect, given that they were so similar,
the two data sets were pooled in order to generate the best
estimate of the repetition-priming effects. All effects noted
were present and were very similar in both of the two data
sets when they were considered separately.
Repetition effects
To address the question of repetition priming, regions in the
left frontal cortex (centred on x ⫽ –37, y ⫽ 9, z ⫽ 37), the
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Fig. 7 fMRI of visually cued word-stem completion and verb generation. Data from experiment 2b show the pathway of brain regions
activated during (A) word-stem completion compared with fixation, (B) verb generation compared with fixation and (C) for the
repetition-priming effect in which all NEW item blocks were directly compared with all OLD item blocks. The format and colour scale
are the same as in Fig. 3 with the threshold set to P ⬍ 0.0001. A and B reveal highly similar patterns of activation, which were also
quite similar to those of experiment 1c (Fig. 3). A subset of activated regions showed repetition-priming effects as revealed in C. The
most prominent included the left inferior frontal gyrus (labelled D and E) and the visual extrastriate regions extending into inferior
temporal cortex (labelled F).
inferior temporal cortex (centred on x ⫽ –50, y ⫽ –58, z ⫽
–12) and the lingual gyrus at or near the primary visual
cortex (centred on x ⫽ –12, y ⫽ –99, z ⫽ –12) were
examined for regional signal intensity change over time (Fig.
8). All regions showed an effect of item repetition, with a
qualitative decrease in magnitude as the repetitions increased.
The signal intensities increased abruptly upon presentation
of NEW items in the last two blocks, establishing that
the signal reductions were related to item-specific factors,
consistent with the behavioural repetition-priming effects
observed in experiment 2a.
Statistical activation maps from the direct comparison
between the NEW item blocks and REP item blocks revealed
the network of brain regions showing priming-related
reductions (Fig. 7C). Two notable findings emerged. First,
confirming the observations from the regional analyses above,
the left frontal and visual extrastriate regions extending
into the inferior temporal cortex showed significant signal
modulation between NEW and REP items, exhibiting greater
activity during the NEW item blocks. Secondly, the network
of regions showing significant reductions comprised only a
subset of those regions activated by the task when compared
with fixation. That is, a subset of regions activated by the
word-stem and word-generation tasks showed significantly
reduced activation in association with item repetition
although, qualitatively, most regions showed some degree of
modulation. The regions showing robust signal reductions
included the left frontal and inferior temporal regions but,
consistent with prior PET and fMRI studies, did not include
regions at or near the primary motor cortex or many of the
visual regions activated during the task. However, unlike our
previous study using randomly intermixed event-related trials
(Buckner et al., 1998a), the present study did reveal significant
left-lateralized signal modulation at or near the primary visual
cortex, perhaps reflecting a form of perceptual priming or
decreased attention to items in the repeat blocks.
In general, the blocked-task paradigm used in the present
study showed a subtle degree of repetition-related modulation
in almost all of the time-courses that were examined.
Moreover, blocked-trial modulation was also observed in the
last new trial block in the POST repetition period within
many regions, the second NEW trial block showing a signal
fMRI evidence for amodal components of priming
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Fig. 8 fMRI signal changes in experiment 2b for three separate regions [A, left inferior frontal gyrus (–37,
9, 37); B, fusiform/inferior temporal gyrus (–50, –58, –12); C, lingual gyrus (–12, –99, –12)]. The timecourse of regional signal change is shown in a format similar to that of Fig. 4. Clear effects of item
repetition were observed during the REP phase. Importantly, the effects were not due to a shift in baseline,
as the extra NEW block in the PRE phase allowed the baseline signal to reach a steady state (seen best in
the lingual gyrus region). Furthermore, following the last repetition block (REP4), the signal change
increased in the NEW blocks during the POST phase, suggesting that the effects were, in part, itemspecific.
reduction relative to the first (Fig. 8). This fMRI signal
reduction for new item blocks paralleled the numerical trends
in the behavioural findings in all but one of the POST blocks
tested (Figs 5, 6, 9 and 10). The tentative conclusion, which
will need to be explored further, is that two separate effects
may exist: a non-specific blocked factor that perhaps relates
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Fig. 9 Repetition priming for auditory word-stem completion.
Data are shown for the auditory variant of word-stem completion
of experiment 3a. The pattern of responding was very similar to
that found for visual word-stem completion (Fig. 5) and verb
generation (Fig. 6).
activity reductions may reflect perceptual aspects of the task.
On the other hand, auditory word processing tasks have
activated these regions, suggesting that their role may be
related to lexical/semantic aspects of the task and, hence,
reflect amodal processes (Price et al., 1996; Binder et al.,
1997; Buchel et al., 1998). To explore which of these
possibilities best characterizes activity reductions related to
frontal and inferior temporal priming, a series of further
studies was conducted using auditory cue presentation. The
hypothesis was that auditory cues would show repetitionpriming effects and that brain regions that showed overlapping
repetition-priming effects between visually and auditorily
cued word-stem completion would reflect amodal processes
relating more to conceptual processes than to perceptual
processes.
Experiment 3a: auditorily cued overt word-stem
completion
Fig. 10 Overt and covert auditory word-stem completion.
Behavioural data from experiment 3b replicate the overt testing
procedure of experiment 3a (Fig. 9) and extend the observation of
a repetition-priming effect to a covert production procedure.
Filled squares indicate overt blocks; open squares indicate covert
blocks. As with the visual cues, the aurally cued task showed
clear repetition-priming effects with covert production.
to the subjects’ anticipation of trials and general arousal level
(possibly related to the participants’ adoption of a general
task ‘set,’ in which the ‘set’ subtly changes for blocks
comprising repeated items relative to blocks comprising
entirely new items), and an item-specific factor.
An open question concerns the degree to which activity
reductions reflect facilitation of (i) amodal, non-specific
processes relating to lexical/semantic search and access or
(ii) perceptual processes dependent on the modality and form
of the cue. For regions such as those in the frontal cortex
that have been associated with higher-level lexical and
semantic processes, the strong hypothesis would be that
reductions occur in these regions independent of cue modality.
However, for other regions, such as the region in the inferior
temporal cortex, the predictions are less clear. On the one
hand, the inferior temporal cortex is contiguous with visual
regions late in the ventral visual processing pathway, and
Experiments 3a–c examined auditorily cued word-stem
completion (e.g. Bassili et al., 1989; Schacter and Church,
1992) in a paradigm structured in the same manner as
experiment 1c (16 s blocks). In this instance, however, all
word stems (single syllables) were presented aurally (e.g. the
sound ‘pur’ or ‘tray’) and participants generated completions
based on the sounds (e.g. ‘perfect’, ‘trait’). The goal of these
studies was to generalize findings from the word-generation
tasks outside the domain of purely visual stimulus
presentation and to determine which brain regions involved
in word generation were activated independently of cue
modality and which were selective for cue modality.
Experiments 3a and 3b were behavioural studies involving
overt word generation and both overt and covert word
generation respectively; experiment 3c involved fMRI
imaging during covert performance of the auditorily cued
word-generation task.
Possible auditory word-completion stems were selected
using the Oxford Psycholinguistic Database. An initial pool
of items was compiled such that all stems were unique and
had at least five English language phonetic completions. A
word corresponding to each stem was recorded in a male
voice using MacRecorder and then edited (using SoundEdit
Pro) to include only the first syllable. A normative study
with 40 participants, aged 16–26 years, showed that the
average correct completion rate for the 147 stems eventually
selected, under untimed presentation conditions, was 88%.
The word stems were presented in five runs, preceded by
a brief practice block. Each run consisted of eight blocks,
each block comprising seven trials. The nature of the task
blocks followed a pattern directly parallel to that of the
visual word-stem completion and verb-generation tasks of
experiment 2a. The actual presentation duration of the
auditory word stems varied somewhat, depending on the
item (i.e. the stems were self-terminating), with a stimulus
presentation rate of one word stem every 2.29 s. Subjects
fMRI evidence for amodal components of priming
visually fixated on a central fixation point during the entire
run to reduce eye movements.
Experiment 3a: results
The average voice onset latencies for overtly generated items
on the auditory cued task are shown in Fig. 9. The pattern
is very similar to that previously observed for both visually
cued word-stem completion and visually cued verb
generation: responses to the NEW items at the outset of the
runs (1403 and 1433 ms) were slower than those to the REP
items, response latencies decreasing to 1298 ms by the fourth
repetition but returning to the initial levels (1432 and 1390
ms) when entirely NEW items were once again presented.
A repeated measures ANOVA, considering only items from
the repetition phase that were the same across the blocks
(i.e. NEW, REP1, REP2, REP3, REP4), revealed a highly
significant effect of repetition [F(4,44) ⫽ 11.22, P ⬍ 0.0001].
Examination of the response times for the four blocks of
NEW items also showed a trend towards an overall effect of
block [F(3,33) ⫽ 2.88, P ⫽ 0.5]; however, from Fig. 9 it
can be seen that this outcome primarily reflected relatively
longer response latencies for the second and third NEW
blocks relative to that for the first and last NEW blocks.
Consistent with this, a focused comparison contrasting the
mean for the first two blocks of NEW items in each run
against the mean for the last two blocks of NEW items
revealed no effect [F(1,11) ⬍ 1].
Consideration of participants’ responses showed a
considerable level of response stereotypy, with an average
of 75% of the items repeated (SD ⫽ 0.13, range ⫽ 0.54–0.91).
Experiment 3b: auditorily cued overt and covert
word-stem completion
The purpose of this experiment was to ensure that covert
auditory stem completion also resulted in repetition priming.
The experimental procedure was identical to that of
experiment 2a except that, for some of the runs, participants
responded covertly rather than overtly. The covert runs
followed the same general pattern as the overt runs in the
visually cued task: an initial ‘estimation’ of the novel
completion rate provided by a preobservation, then silent
(covert) production until the fourth repetition, which was
spoken, and ending with two blocks of new items, both
requiring spoken responses. Each subject had two runs in
which responding was entirely overt and three runs involving
a covert response. As in the visually cued word-stem
completion paradigm, participants were instructed,
immediately before each block (via the presentation of a
visual cue), whether the block was to be ‘spoken’ or ‘silent.’
Experiment 3b: results
Clear priming effects of repetition on auditory word-stem
completion were again observed (Fig. 10). For the overt runs,
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considering only the items from the repetition phase that
were the same across the blocks (i.e. NEW, REP1, REP2,
REP3, REP4), response latencies decreased from 1393 ms
on the first presentation to 1224 ms on the fourth repetition
[F(4,44) ⫽ 3.88, P ⫽ 0.009]. Most importantly, a similar
decrement was observed for runs in which participants
responded covertly, the estimated response latency for the
PRE baseline items of 1449 ms decreasing to 1168 ms by
the fourth repetition [F(1,11) ⫽ 27.96, P ⫽ 0.0003]. Response
latencies to NEW items during the POST phase were similar
to those for NEW items in the PRE phase, with similar
increases in response times for the new items observed in
runs that were preceded by overt or by covert response
generation, thereby showing, in both instances, that the
reduction in voice onset latencies was specific to the particular
items that were presented.
The average level of stereotypy for the overt runs was
very similar to that observed for the previous auditory
stem-completion experiment, in which participants responded
overtly for all runs (mean response stereotypy of 77%, SD ⫽
0.14, range ⫽ 0.51–0.96).
Experiment 3c: fMRI of covert auditorily cued
word-stem completion
Functional imaging was performed during covert word
generation, using procedures similar in format to behavioural
experiment 3a and similar in terms of fMRI format to
experiment 2b. Again, prior to each run specific instructions
were given to perform all task blocks covertly, in this
instance blocks of auditorily cued word-stem completion.
Five functional runs were acquired per subject, each run
consisting of 16 interleaved 16 s blocks (TR ⫽ 2 s). Within
all runs, word-stem completion blocks followed the same
order as in experiment 2a (NEW, NEW, REP1, REP2, REP3,
REP4, NEW, NEW), and regularly alternated with blocks of
visual fixation (odd numbered blocks). Stimulus duration
varied during task blocks, with 2.3 s between onsets (seven
items per block).
Experiment 3c: results
Main effect of task
Multiple brain regions forming a network were active during
auditory word-stem completion when compared with visual
fixation (Fig. 11A, Table 2). Many of these regions had also
been found to be activated during the visual word-stem
completion and verb-generation tasks, including the left
inferior frontal gyrus near the border of BA 6 and/or 44
extending ventrally into the inferior prefrontal cortex at or
near BA 44, 45 and/or 47 near the frontal operculum.
Activations were again noted in the supplementary motor
area and the right lateral cerebellum.
Quite distinct from the visual tasks, however, the auditory
variant showed extremely robust activation in the bilateral
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Fig. 11 fMRI of aurally cued word-stem completion. Data from experiment 3c show the pathway of brain regions activated during
(A) auditory word-stem completion compared with fixation, and (B) for the repetition-priming effect in which all NEW item blocks were
directly compared with all OLD item blocks. The format and colour scale are the same as in Figs 3 and 7. A pathway of brain regions is
activated overlapping in part with those observed during experiments 1c and 2b including activation of the left inferior frontal gyrus
(labelled A, D and E) and a limited region of the inferior temporal gyrus (labelled G). Activation of the visual cortex is largely absent;
in fact it is decreased (see Fig. 13). The auditory cortex is robustly activated bilaterally (labelled F). The repetition-priming effect (B) is
again present in the left frontal cortex and also within the left inferior temporal cortex.
auditory cortex. This activation was detected in spite of the
loud sound of the scanner, which may have interacted with
the word stems, consistent with earlier observations (Binder
and Rao, 1994).
Regions in the visual cortex extending into the inferior
temporal cortex and parahippocampal gyrus showed two
opposing effects that existed in spatially distinct regions. By
and large, the visual cortex was either silent or had reduced
activation compared with fixation (Fig. 12). Such reductions
are distinct from those observed during item repetition. In
this instance, the reductions are in relation to fixation and
not relative to an active task baseline with an elevated activity
level due to task demands. The reductions here probably
(although not definitively) reflected a cross-modal suppression
effect: strong activation in the auditory cortex may have been
suppressing activity in certain visual regions (Haxby et al.,
1994; Kawashima et al., 1995; Buckner et al., 1996b; for
review, see Shulman et al., 1997). The visual regions showing
activity reductions were extremely similar in spatial location
to those previously observed with PET during auditory word
presentation (Buckner et al., 1996b).
The second effect observed in the putative visual cortex
was surprising: a region in the inferior temporal cortex near
the fusiform gyrus (x ⫽ –43, y ⫽ –52, z ⫽ –12) was
increased in activation and spatially distinct from nearby
regions of signal decrease that extended into the
parahippocampal cortex and posteriorly into the visual
extrastriate regions. The time-course of activation of this
inferior temporal region, which is quite similar in location
to the region showing activity reductions in the visually
cued tasks, is shown in Fig. 13. Thus, auditory word-stem
completion increases activity within certain regions of the
inferior temporal cortex in addition to a more widespread
and general suppression effect across many regions of the
ventral visual processing pathway. The clear opposing effects
of the auditory word-stem completion task on the separate
occipital-temporal regions shows that they are functionally
dissociable regions (Fig. 12). The inferior temporal region
behaved as an amodal processing region.
Repetition effects
In a parallel analysis of the visual word-stem completion
studies, regions in the left frontal cortex (centred on x ⫽
–40, y ⫽ 6, z ⫽ 34), the inferior temporal cortex site of
activation increase (centred on x ⫽ –43, y ⫽ –52, z ⫽ –12)
and the superior temporal gyrus at or near the primary
auditory cortex (centred on x ⫽ –62, y ⫽ –18, z ⫽ 12) were
examined for regional signal intensity change over time (Fig.
13). Both the frontal and inferior temporal regions showed
strong effects of item repetition similar in profile and
magnitude to those observed in the earlier studies using
visual cues. For both regions, the reductions in signal intensity
were reversed upon presentation of NEW items, again
indicating that the signal reductions related to item-specific
factors. By contrast, the region near the primary auditory
cortex showed no change that was associated with itemspecific repetition effects. Thus, despite the finding that
regions at or near the primary auditory cortex were the most
robustly activated (in terms of both statistical significance
fMRI evidence for amodal components of priming
Fig. 12 More detailed fMRI images obtained during auditory
word-stem completion. The behaviour of regions along the ventral
visual processing pathway extending into the inferior temporal
cortex from experiment 3c is revealed. Horizontal images show
both the increases (red/yellow) and decreases (blue/green) in
activation; the level of the horizontal section is indicated at the
bottom. The threshold is set to P ⫽ 0.001; increasing colour
intensity indices increasing significance. Note the clear opposing
behaviour of the more posterior and anterior regions. The more
posterior regions (B) show clear reductions in activation
consistent with a cross-modal suppression effect. By contrast, the
more anterior region (A; x ⫽ –43, y ⫽ –52, z ⫽ –12) is
significantly activated by the task in a manner similar to that of
the frontal cortex.
and percentage signal change), these regions showed little
or no modulation in relation to repetition priming. Direct
comparison of the NEW with the REP item blocks confirmed
all of these findings (Fig. 11B).
General discussion
The present series of studies explored the effects of item
repetition during a variety of lexical/semantic wordgeneration tasks. Tasks included visually cued word-stem
completion, visually cued verb generation and aurally cued
word-stem completion. In all instances, behavioural
measurements of voice onset latency demonstrated that
repetition of items decreased response latency (repetition
priming). Reductions in response latency followed a
stereotypic pattern that was predicted well by a power
function. Blood oxygenation level-dependent-contrast fMRI
measurements revealed that repetition of items was associated
with decreased activity levels within specific brain regions
635
that were activated by the tasks in their unprimed states,
including the left frontal cortex near the inferior frontal gyrus
and also the inferior temporal cortex. All correlates of item
repetition were reversible upon presentation of novel items,
indicating that the effects were item-specific. Taken
collectively, the present findings support a neural correlate
of repetition priming: repeated exposure to an item leads to
facilitated (speeded) processing of that item, which correlates
with anatomically selective reductions in brain activity (see
also Squire et al., 1992; Raichle et al., 1994; Buckner et al.,
1995a; Demb et al., 1995; Blaxton et al., 1996; Gabrieli
et al., 1996; Schacter et al., 1996; for review see Schacter
and Buckner, 1998).
The observation of close parallels between the patterns of
behavioural facilitation (indexed by voice-onset latencies)
and the patterns of neural activation (anatomically selective
reductions) as a function of repetition across three types of
tasks—visually cued word-stem completion, visually cued
verb generation and aurally cued word-stem completion—
focuses attention on the commonalties of the tasks and the
similar processes involved. All three tasks required the
selection and retrieval of a word that met certain constraints.
The nature of the constraints differed for the three tasks—
primarily orthographic and phonological for visually
presented word-stems, phonological for aurally presented
word-stems, and semantic, conceptual or associative for verb
generation. However, in each instance, a number of alternative
responses were possible, and the participant needed to ‘select’
and ‘retrieve’ one of those responses (Thompson-Schill
et al., 1997).
All three tasks activated a network of shared regions,
including the ventral and dorsal regions of the left inferior
frontal gyrus (BA 44/45/47 and 6/44), which are thought to
be involved in operating on and/or maintaining higher-level
verbal representations (i.e. semantic, lexical or phonological
information). Decreases in brain activity in these frontal
regions may provide neural evidence for a relatively ‘nonspecific’ or ‘amodal’ component that has been repeatedly
documented in behavioural studies of repetition priming (e.g.
Rajaram and Roediger, 1993) and that may also partially
underlie the facilitation of conceptual processing, in which
the cue that is provided during initial exposure shows no
overlap of perceptual information from study to test, but
requires the retrieval of a specific word or concept (e.g.
Bassili et al., 1989; Blaxton, 1989; see also Demb et al.,
1995; Gabrieli et al., 1996).
This emphasis on amodal components of the word-stem
completion task may seem surprising, particularly given that
word-stem completion priming, studied in its conventional
form, shows a strong perceptual component, as evidenced by
significant modality effects (Roediger and McDermott, 1993;
Schacter, 1994). However, in all previous studies of wordstem completion priming, the study and test task did not
match, and the stimuli did not repeat directly. For example,
Rajaram and Roediger (Rajaram and Roediger, 1993; see
also Squire et al., 1992; Buckner et al., 1995a) showed
636
R. L. Buckner et al.
Fig. 13 fMRI signal changes in experiment 3c for three separate regions similar to those shown in Figs 4 and
8. The time-course of regional signal change is shown. In this instance a region near the primary auditory
cortex [superior temporal gyrus (–62, –18, 12), shown in C] was selected rather than the primary visual
cortex, which was not activated in the auditory variant. Again, clear effects of item repetition were observed
during the REP phase for the region within the left inferior frontal gyrus (–40, 6, 34) (A) and for left inferior
temporal cortex (–43, 52, –12) (B). Following the last repetition block (REP4), the signal change increased
in the NEW blocks during the POST phase, suggesting that the effects were, in part, item-specific in a
manner similar to that seen in the visual task variants.
complete words at study (e.g. ‘basket’), at which time subjects
rated how much they liked the meaning of the word. At test,
word-stem completion was used to assess priming (e.g.
complete ‘bas_’). In our variant, we repeated directly both
word-stem cues (e.g. ‘bas_’) and the task (subjects were
always attempting to complete word-stems), thereby holding
fMRI evidence for amodal components of priming
constant the conceptual, lexical, and semantic retrieval
demands across repetitions and never actually presenting the
full (visual or auditory) form of the word.
It is thus not surprising that results from our variant of the
word-stem completion task were similar to those elicited by
other tasks that directly repeat lexical/semantic retrieval
demands and traditionally show conceptual priming effects
(e.g. the abstract/concrete classification task as studied by
Demb et al., 1995 and the verb-generation task studied by
Raichle et al., 1994). In this regard, the methods and
results of the present study also help to refocus theoretical
interpretations of perceptual versus conceptual priming. A
complex task such as word-stem completion is not exclusively
open to influences in either perceptual or conceptual
processing; by repeating higher-level lexical/semantic
retrieval components of the task, it appears that strong
conceptual priming effects can be enhanced. However, full
interpretation of this finding, and the precise extent to which
the effects of word-stem completion under conditions such
as those used here are more conceptual in nature than those
for a typical word-stem completion task, will have to await
more complete behavioural analysis.
Differences were noted between the auditory and visual
variants of the tasks, which suggested regions that were
more related to perceptual processes. The visual variants, as
expected, showed robust activity increases in the primary
and association visual cortex, whereas the auditory variant
showed a robust bilateral increase near the primary auditory
cortex extending into the auditory association cortex.
Importantly, repetition-priming effects were observed in
several of these modality-specific regions, including regions
near the primary visual cortex (x ⫽ –12, y ⫽ –99, z ⫽ –12).
The finding of a reduction in activity in the primary visual
cortex came as a surprise because event-related fMRI studies
of object repetition have shown that the level of primary
visual cortex activation is preserved in the face of repeated
presentations (Buckner et al., 1998a). Although further
research will need to determine the specific task factors that
account for this difference, one possible explanation is that
the blocked testing procedure allows participants to anticipate
repeated items not on an item-by-item basis, because items
were newly randomized on each presentation, but for the
entire block of items, such that subjects were aware that all
of the items would be new or that all would be repetitions.
This awareness may have in some manner altered attentional
or other aspects of processing. It should be noted, however,
that the inferior frontal gyrus and the inferior temporal
activity region reductions generalize across both blocked and
event-related testing procedures, and across covert and overt
procedures. Thus, there were highly reproducible findings in
these regions, and these are the focus of the remaining
discussion.
Of particular theoretical importance was the finding that a
region in the left inferior temporal cortex was activated by
word-stem completion regardless of the cue modality and,
furthermore, this region had reduced activity in response to
637
item repetition for both visual and auditory cues. Thus,
despite being contiguous with regions in the ventral visual
processing stream, this inferior temporal region behaved in
all respects like an amodal or non-specific processing region.
The most parsimonious explanation for this is that the
region was driven, in part, by top-down modulation, possibly
interdependent with prefrontal activity. The two regions
showed similar repetition-priming effects, and the prefrontal
cortex provides a conduit by which repetition of an auditory
cue could influence inferior temporal cortex activity.
Previously, regions in the inferior temporal cortex showing
item-related activity reductions have been associated with
facilitation in visual perceptual processes (for reviews, see
e.g. Schacter and Buckner, 1998; Wiggs and Martin, 1998).
The present findings suggest that a partial revision of this
explanation is necessary, at least for certain tasks and for
certain regions within the inferior temporal cortex.
Consistent with this idea and with our results, Badgaiyan
and colleagues recently reported a PET study of auditory
word-stem completion priming in which subjects heard a
series of words and were then scanned during primed and
unprimed auditory stem completion (Badgaiyan et al., 1999).
They found that there was decreased blood flow during
primed compared with unprimed auditory stem completion
performance in a region of the extrastriate cortex (BA 19).
This was similar to one of the previous PET studies of visual
stem completion priming that exhibited priming-related blood
flow reductions (Squire et al., 1992; Buckner et al., 1995a;
Schacter et al., 1996; Backman et al., 1997). Although this
region was posterior to the region in the inferior temporal
cortex that showed repetition-related reductions in the present
study (stereotaxic coordinates from experiment 1 of
Badgaiyan et al. are x ⫽ 40, y ⫽ –80, z ⫽ 4; x ⫽ –44,
y ⫽ –82, z ⫽ 4), both studies indicate that regions in or near
the ventral visual processing stream show reductions during
auditory priming and repetition, thereby raising important
questions about the nature and function of those decreases.
However, whereas we found that the inferior temporal region
that showed repetition-related decreases was activated during
baseline task performance compared with fixation, the
extrastriate regions that showed priming-related decreases in
the study of Badgaiyan and colleagues showed neither
increases nor decreases compared with a fixation control.
The contrasting patterns may be attributable to differences
in behavioural paradigms, imaging procedures or the nature
of the regions identified in the two studies.
The inferior temporal region localized in the present study
to x ⫽ –43, y ⫽ –52, z ⫽ –12 may be activated independently
of visual sensory input and may play a role in the formation,
maintenance and/or interlinking of the conceptual lexical/
semantic representations involved during task performance
(see also e.g. Price et al., 1996; Binder et al., 1997). Notably,
in a PET study that also employed auditory presentation but
used the verb-generation task, Warburton and colleagues
found activation in a slightly superior region, both comparing
verb generation against a resting state (peak at x ⫽ –48,
638
R. L. Buckner et al.
y ⫽ –50, z ⫽ –7) and when comparing verb generation with
a verb-noun comparison task (judge whether a presented verb
and noun are appropriately matched, peak at x ⫽ –50, y ⫽
–50, z ⫽ –12) (Warburton et al., 1996). These authors pointed
to several convergent findings from investigations of semantic
dementia (e.g. Hodges et al., 1992) and presurgical
explorations of epileptic patients (e.g. Luders et al., 1991),
as well as lesion and other studies, suggesting that this region
is involved in language processing and, particularly, ‘may
have a key role linking meaning with words’ (Warburton
et al., 1996, p. 173). Bookheimer and colleagues also note
that this region has strong connections with Wernicke’s area
and explicitly suggest that it appears to be important ‘for
naming or verbally ‘tagging’ recognizable stimuli but is not
modality specific’ (Bookheimer et al., 1995).
Evidence from the present investigations suggests that, as
item repetition decreases the demand for manipulating or
interconnecting these (possibly intermediate) lexical or
semantic representations, the activity within inferior temporal
regions may decrease. This places the effect more in line
with ideas of conceptual rather than perceptual (data-driven)
priming. However, at present we can state with certainty
only that the processes engaged are amodal in nature. The
relationship of these amodal processes to traditional notions
of conceptual processes is nonetheless intriguing. Thus, the
situation within the brain may be more complex than was
initially expected (e.g. Schacter and Buckner, 1998), and the
link between perceptual/conceptual processes and between
anterior and posterior brain regions is only now beginning
to be understood. Regions contiguous with regions within
the ventral visual processing stream, such as the inferior
temporal region highlighted by the present series of studies,
may play a role in conceptual repetition priming.
A neural model of conceptual priming suggested by the
present data is that amodal lexical/semantic processes, which
may be triggered initially by modality-specific cues, will
proceed via an interaction between the frontal cortex and
posterior regions, including regions within the inferior
temporal cortex. The interaction between frontal and posterior
regions probably involves a top-down influence. During
lexical/semantic processing tasks, the interaction between
frontal and posterior brain regions decreases in response to
direct item repetition. This reduction is manifested as a
decrease in the blood oxygenation level-dependent-contrast
fMRI signal and faster response times (priming). Thus, the
human brain takes advantage of prior stimulus–response
exposures by reducing the amount of time-consuming
frontally mediated processes required to complete the task.
Such processes may be those that allow a flexible responseselection mode in novel situations that are less relevant when
an item can directly specify a response via prior experience
(Raichle et al., 1994).
Acknowledgements
We thank Terrance Campbell and Mary Foley for technical
assistance, David Ekstrom for recording the auditory stimuli,
Lissa Galluccio for help in the behavioural studies and in
collecting normative data, and Steven Petersen, Anders Dale
and Marcus Raichle for valuable suggestions during the
development of this research. This work was supported by
the National Institute of Mental Health grant 57506 to R.L.B.,
National Institute of Deafness and Communication Disorders
grant 03245 to R.L.B. and National Institute on Aging grant
08441 to D.L.S.
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Received March 26, 1999. Revised August 20, 1999.
Accepted September 20, 1999